Biochemical effects of nitric oxide-related toxicity on drug-metalbolizing flavin-containing monooxygenase(FMO)system

초록

Hepatic drug metabolism function is known to be depressed in patients infected with bacteria,parasites and virus.Suppression of hepatic cytochrome P450(CYP) and flavin-containing monooxygenase(FMO) activities observed both in acute and chronic liver diseases is known to be the major cause of drug overdose toxicities in clinics.Under a septic condition caused by infectious agents, along with the inflammatory stimulation,large quantities of endotoxins and cytokines like interferon and intereukines are produced. These observations suggest that NO is an important mediator involved in the regulation of FMO mRNA expression in vivo and further that the overproduced NO can inhibit the FMO activity by nitration and the CYP activity by nitrosylation. Therfore, the overproduced NO caused by sustained induction of iNOS appears to be responsible for the decreased hepatic drug metalbolism function observed generally under septic(over-immune)conditions caused by systemic bacterial, viral or parasitic infections.